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Biomedical subjects

A C Darke

Publications and source records attributed to A C Darke.

32 records · Page 2Linked to original sources
PubMed1986

Respiratory and cardiac effects of metoprolol and bevantolol in patients with asthma.

The effects on standing heart rate and respiratory function of two relatively selective beta 1-adrenoceptor antagonists, metoprolol and bevantolol, were compared in a double-blind, randomized, crossover study of 16 patients with asthma. After control observations on 2 separate days, the patients received approximately equivalent cardiac beta-adrenoceptor antagonist doses of metoprolol, 12.5, 25, 50, and 100 mg, and bevantolol, 18.75, 37.5, 75 and 150 mg, at intervals of 2 hours. Dosing was stopped if symptoms warranted or if there was a fall of greater than or equal to 20% in the forced expiratory volume in 1 second. In general, the cumulative dosing regimen proved a safe and effective means of assessing bronchial responsiveness to these beta-blockers in asthma, but one patient had to be dropped from the study because of severe bronchoconstriction after the first dose. Of the 15 patients studied who were taking both drugs, seven patients were withdrawn prematurely. In these seven patients, the average maximum tolerated cumulative doses were 45.5 mg bevantolol and 26.8 mg metoprolol, doses that are much lower than those usually required for therapeutic activity. The respiratory response to either drug could not be predicted.

Administration, Oral↗
PubMed1986

Lowering of plasma isoxicam concentrations with acetylsalicylic acid.

The pharmacokinetics of isoxicam 200 mg administered orally in 10 healthy male volunteers was studied before and during administration of acetylsalicylic acid 3.9 g daily by mouth starting 5 days after isoxicam. There was a statistically significant decrease in plasma isoxicam concentrations, but no significant change in time to reach maximum plasma concentration or disappearance time. The mechanisms of this interaction is probably competitive displacement of isoxicam from albumin by acetylsalicylic acid or salicylate. These results are consistent with the known effect of ASA in producing competitive displacement of other protein bound antiinflammatory drugs.

Administration, Oral↗
PubMed1983

Open safety-in-use trial of a new high-potency antacid product.

In an open safety-in-use study, the subjective effectiveness and taste acceptability of a new high-potency antacid product were compared to previous treatment in 109 patients presenting with upper gastro-intestinal disorders of functional origin. Severity of the dominant symptoms prior to treatment was compared with that of symptoms present during treatment. Sixty-seven per cent to 73% of upper gastro-intestinal tract symptoms were completely relieved. Eighty-three per cent versus 48% of patients seen in a private practice setting, as compared with the speciality practice, reported good to excellent results, with 92% versus 56% describing good to excellent taste acceptability. When compared with previous antacid therapy, 70% of the patients preferred the new high-potency formulation to the regular-strength products, for both effectiveness and taste. The incidence of product-related side-effects was low, with only 6.7% experiencing the diarrhoea or loose stools commonly associated with conventional products containing magnesium hydroxide.

Adolescent↗
PubMed1982

Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy.

The effects of different oral doses of isosorbide dinitrate administered acutely and four times daily during sustained therapy were studied in 12 patients with angina pectoris. After administration of 30, 60 and 120 mg of isosorbide dinitrate, the average plasma concentrations were higher and the area under the plasma concentration time curve was greater during sustained than during acute therapy (p less than 0.01). Reduction in standing systolic blood pressure was greater during acute than during sustained therapy (p less than 0.001). This reduction in systolic blood pressure was dose-related and persisted for 8 hours during acute therapy, but was not dose-related and was demonstrable for only 4 hours during sustained therapy. Compared with placebo therapy, exercise duration to the onset of angina and to the development of moderate angina increased significantly after each dose of isosorbide dinitrate for 8 hours during acute therapy but for only 2 hours during sustained therapy. During acute therapy, administration of a single dose of 15 or 30 mg of isosorbide dinitrate produced similar improvement in exercise tolerance as did a dose of 60 or 120 mg. During sustained therapy (15 mg four times daily), exercise tolerance increased to the same magnitude as with doses of 30, 60 or 120 mg four times daily. In most patients, near maximal improvement in exercise tolerance occurred after a dose of 15 or 30 mg four times daily. It is concluded that during sustained therapy with isosorbide dinitrate, partial tolerance to the antianginal and circulatory effects develops rapidly.

Administration, Oral↗
PubMed1978

Comparison of oxazepam, flurazepam and chloral hydrate as hypnotic sedatives in geriatric patients.

In a four-week study, a comparison was made of oxazepam, flurazepam and chloral hydrate as hypnotic sedatives in 17 geriatric patients. Each drug was given alone for six nights, with a two-night placebo interval following each phase. Each patient completed an additional placebo phase (up to six nights) before each drug phase. The number of awakenings per night and the sleep latency (time required to fall asleep) were determined from the patients' reports and from the reports of a nurse-observer. Only for oxazepam was the number of patient-reported awakenings per night significantly less than for placebo, although with both oxazepam and flurazepam the awakenings were fewer than with chloral hydrate. According to the patient-reports, sleep latency was significantly lower with flurazepam than with placebo; for oxazepam and chloral hydrate the latencies were not significantly different from those for flurazepam or placebo. Only for oxazepam were the patients' ratings of sleep quality significantly greater than for placebo. The objective assessment of sleep by the nurse-observer usually confirmed the patients' assessments. Morning drowsiness was the most common side effect, reported equally for placebo and for the active drugs. Drowsiness during the day was reported less frequently for oxazepam than for flurazepam, chloral hydrate or placebo. It is concluded that oxazepam is safe and efficacious for the short-term management of insomnia in the elderly.

Aged↗
PubMed1976

Critical opening pressure and reactivity of tail vessels in conscious hypertensive rats.

The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA-NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA-NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA-NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP.

Angiotensin II↗
PubMed1973

The effect of chronic duct ligation on the vascular and secretory responses of the cat's submaxillary gland.

1. The object of the present experiments was to re-investigate the role of kallikrein in functional hyperaemia in the submaxillary gland of the cat. Kallikrein concentration in the gland and saliva was reduced by ligation of the duct for 2-3 days before the acute experiment, at which time the duct was cannulated proximal to the ligation and blood flow and salivation measured.2. Despite the fall in kallikrein concentration, a normal two-phase vascular response was obtained on continuous stimulation of the chorda-lingual nerve at 1-5 Hz and the progressive increase in blood flow to a constant level characteristic of 10 and 20 Hz stimulation was also seen. Quantitatively, the increase in blood flow following a 10 sec stimulation was reduced to about 75% of control values at all stimulation frequencies used and the maintained vasodilatation was reduced when using continuous stimulation at 1 Hz but not at 10 and 20 Hz.3. The supersensitivity to the vasodilator properties of bradykinin, previously reported to follow duct ligation, was confirmed.4. The increased blood flow produced by chorda-lingual nerve stimulation could be delayed by circulatory arrest. Evidence was obtained suggesting that the vascular response to chorda stimulation delayed by arterial occlusion was not mediated by kallikrein alone.5. It was concluded that kallikrein was not the sole mediator of functional hyperaemia in the cat submaxillary gland but that a combination of vasodilator nerves and kallikrein release explained more phenomena than either hypothesis alone.

Acetylcholine↗
PubMed1972

Dependence of functional vasodilatation in the cat submaxillary gland upon stimulation frequency.

1. Submaxillary gland blood flow and salivation have been measured in anaesthetized cats and the chorda-lingual nerve has been stimulated at different frequencies.2. At low stimulation frequencies (1-5 Hz) there was a large transient increase in blood flow followed by a more modest maintained increase which lasted as long as stimulation continued. Stimulation at 10-20 Hz also produced a rapid initial increase in flow but at these frequencies the subsequent decline was not seen and a gradual further increase to a maintained level was observed.3. Atropine in small doses depressed both the transient and the maintained response to low frequency stimulation but at 10-20 Hz the maintained vasodilatation was unaffected by the drug.4. The transient increase in potassium concentration in saliva and venous blood draining the gland was not correlated with the vascular response.5. In conclusion, further details have been provided concerning the vascular response to chorda-lingual nerve stimulation and its sensitivity to atropine. Functional vasodilatation is not secondary to potassium release and is not due to a direct interaction between rate of saliva production and rate of blood flow although the vasodilatation does appear to be related in part to the acompanying salivation.

Animals↗
PubMed1971

Myoepithelial cell activation in the submaxillary salivary gland.

1. Pressure in the duct of the submaxillary gland of the cat was recorded under chloralose anaesthesia. Single pulses applied to the parasympathetic nerve caused a pressure rise.2. Salivation was just detectable in about half of the animals when an open tube was connected to the duct and single pulses applied to the nerve. Applying a back pressure of 1-4 mm Hg renders the duct less distensible and under these circumstances secretion of 1-3 mul. fluid was always seen. An alternative method of detecting salivation based on the pressure record itself also showed that salivation occurred in response to the stimulus and that salivation was responsible for the pressure rise observed.3. Single pulses applied to the cervical sympathetic trunk produced a small fall in pressure. In a short series of pulses this was followed by a slow rise which then slowly decayed. It was tentatively concluded that the initial fall was secondary to the accompanying vasoconstriction but the subsequent effects were due to myoepithelial cell contraction.4. Close arterial injection of bradykinin caused a pressure rise which could best be explained by myoepithelial cell contraction.5. It is concluded that the myoepithelial cells of the submaxillary gland of the cat do not receive a parasympathetic motor innervation but it is probable that they are innervated by the sympathetic nervous system and contract in the presence of bradykinin.

Anesthesia, General↗